Effect of Paracetamol on Kidney Function in Severe Malaria

NCT04251351 | Unknown Phase 3 DMC

• 1 other identifier: H19-03570
• Study Type: interventional
• Target: 460
• Locations: 1 country
• Sites: 1

Brief Summary

A randomised open labeled, parallel-group, controlled trial to assess the efficacy of paracetamol to reduce kidney dysfunction caused by cell-free haemoglobin-mediated oxidative damage in paediatric patients with falciparum malaria complicated by intravascular haemolysis.

Conditions

Severe Malaria; Malaria,Falciparum; Acute Kidney Injury; Paracetamol

Keywords

Severe Malaria; Falciparum; Paracetamol; Renoprotection; Acute Kidney Injury

Outcome Measures

Primary Outcomes (2)

• Acute kidney injury (AKI) or death among patients enrolled without AKI (Composite outcome)

  Composite outcome of development of AKI (defined as creatinine ≥26.5 µmol/L or ≥1.5x baseline), or death at any timepoint

  during first 7 days of enrolment

• Acute kidney injury (AKI) progression or death among patients enrolled with AKI (Composite outcome)

  Composite outcome of worsening of AKI (defined as creatinine ≥2x baseline, or ≥3x baseline, or initiation of RRT or eGFR \<35 ml/min/ 1.73 m2) or death at any timepoint.

  during first 7 days of enrolment

Secondary Outcomes (21)

• Number of patients with serious adverse events

  AST/ALT/total bilirubin during the first 5 days from enrolment; mortality assessed Day 0 to 7.

• Proportion of patients who develop Major Adverse Kidney Events (MAKE) composite

  90 days

• Fever clearance time

  6-hourly temperature assessments during first 7 days from enrolment

• Coma recovery

  6-hourly GCS/BCS assessments during first 7 days from enrolment

• Longitudinal change in renal function

  During the first 7 days from enrolment

Study Arms (2)

Arm 1

EXPERIMENTAL

Paracetamol 15 mg/kg/dose 6 hourly for 72 hours

Drug: Paracetamol

Arm 2

SHAM COMPARATOR

Mechanical antipyresis (i.e. loose clothing, tepid sponging, fanning and cooling blanket) if fever in the first 72 hours.

Procedure: Mechanical antipyresis

Interventions

Paracetamol DRUG

Paracetamol 15 mg/kg/dose IV 6 hourly for 72 hours

Also known as: Acetyl-Para-Aminophenol (APAP), Acetaminophen

Arm 1

Mechanical antipyresis PROCEDURE

Mechanical antipyresis (i.e. loose clothing, tepid sponging, fanning and cooling blanket) if fever in the first 72 hours. If a temperature \>38.5°C persists despite mechanical antipyresis, or if deemed necessary by the treating clinician, then paracetamol can be administered according to local practice (paracetamol IV 15 mg/kg as needed).

Arm 2

Eligibility Criteria

• Age: 1 Year - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or Female, patients aged 1 to ≤ 14 years
• Severe P. falciparum malaria, confirmed by positive blood smear with asexual forms of P. falciparum or positive PfHRP2 rapid diagnostic test (RDT).
• Pre-specified modified criteria for severe falciparum malaria
• Upon hospital admission, asexual parasitaemia plus at least ONE of the following:
• Glasgow coma score \< 11/15 or Blantyre coma score \<3/5 in pre-verbal children
• Generalized convulsions (≥2 in 24 hours)
• Jaundice (visible jaundice)
• Severe anaemia (HCT \<15%/Hb\<5 g/dL: aged \<12) Severe anaemia (HCT \<20%/Hb\<7 g/dL: aged ≥12)
• Hyperparasitaemia (\>10%)
• Hypoglycaemia (glucose \< 2.2 mmol/L; \<40 mg/dL)
• Kidney dysfunction (blood urea \> 20 mmol/L)
• Acidosis (venous bicarbonate \<15 mmol/L or base excess less than -3.3mEq/L)
• Venous lactate \> 5 mmol/L
• Shock (systolic blood pressure \< 70 mmHg (\<12 years) \<80 mmHg (≥12 years) with cool extremities or capillary refill \>3 seconds)
• Respiratory distress (costal indrawing, use of accessory muscles, nasal flaring, deep breathing or severe tachypnea (respiratory rate\>ULN for age)

You may not qualify if:

• The participant may not enter the trial if ANY of the following apply:
• Contraindication or known allergy to paracetamol
• Known chronic liver disease or tender hepatomegaly
• Known chronic kidney disease, history of renal replacement therapy or renal biopsy
• Participants who are already enrolled in another research trial involving an investigational product or have participated to the same study before

Sponsors & Collaborators

• University of British Columbia: lead
• Mahidol Oxford Tropical Medicine Research Unit: collaborator
• Kinshasa Medical Oxford Research Unit: collaborator

Study Sites (1)

The Kinshasa Medical Oxford Research Unit (KIMORU)

Kinshasa, Congo, Democratic Republic of the Congo

RECRUITING

MeSH Terms

Conditions

Malaria; Malaria, Falciparum; Acute Kidney Injury

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Katherine Plewes, Dr.

  Mahidol Oxford Tropical Medicine Research Unit

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katherine Plewes, Dr.

CONTACT

+1-604-603-4033; katherine@tropmedres.ac

Arjen Dondorp, Prof.

CONTACT

+662-203-6333; arjen@tropmedres.ac

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Prior to randomization, participants will be stratified into two groups: (i) Patients with no acute kidney injury (AKI) at enrolment, and (ii) Patients with AKI at enrolment. Both groups will be randomised into two arms: Arm 1: Paracetamol 15 mg/kg/dose 6 hourly for 72 hours Arm 2: Mechanical antipyresis

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: January 31, 2020
• Study Start: December 13, 2021
• Primary Completion: June 1, 2024
• Study Completion: November 1, 2025
• Last Updated: June 13, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: After completion of trial activities and reporting
• Access Criteria: MORU Data Sharing Policy. (http://www.tropmedres.ac/data-sharing-policy)

Locations

DE (1)